Faulty DNA repair can lead to increased mutations, formation of cancers, and cell death. The process by which repair proteins find damaged bases within the DNA represents an important type of protein- DNA interaction, which is not well-understood. The UvrA, UvrB,and UvrC proteins work together to identify and remove DNA damage in a process called nucleotide excision repair. One of the most remarkable aspects of NER is that it can remove a wide range of DNA lesions that differ in chemistry and structure. The UvrABC proteins are believed to recognize the damage-induced distortion in the DNA helix rather than the lesion per se. However, detailed studies of the kinetics,thermodynamics and structural aspects of the Uvr proteins have been limited due to the lability and instability of the proteins. To overcome this problem we have recently cloned and overexpressed UvrA, UvrB,and UvrC from the thermophile, Bacillus caldotenax. The proteins maintain their activity at 65oC and are more amenable to structural and biophysical studies. Work is underway to understand the structure and function of these proteins using x-ray crystallography, stopped-flow fluorescence and site-directed mutagenesis. - DNA, Recombinant, Escherichia Coli Site- directed mutagenesis Polymerase Chain Reaction, Protein Conformation Protein Structure, Sequence Analysis, DNA Structure-Activity Relationship